miR-106b-5p promotes aggressive progression of hepatocellular carcinoma via targeting RUNX3

Cancer Med. 2019 Nov;8(15):6756-6767. doi: 10.1002/cam4.2511. Epub 2019 Sep 10.

Abstract

Background and objectives: The roles of microRNA(miR)-106b-5p in hepatocellular carcinoma (HCC) remain unclear. We aimed here to investigate the clinical significance of miR-106b-5p expression in HCC and its underlying mechanisms.

Methods: Expression levels of miR-106b-5p in 108 HCC clinical samples by quantitative real-time reverse transcription PCR. Associations of miR-106b-5p expression with various clinicopathological features and patients' prognosis were evaluated by Chi-square test, Kaplan-Meier, and Cox proportional regression analyses, respectively. The target gene of miR-106b-5p and their functions in HCC cells were investigated by luciferase reporter, CCK-8, and Transwell Matrigel invasion assays.

Results: miR-106b-5p expression was markedly higher in HCC tissues than in noncancerous adjacent liver tissues (P < .001). miR-106b-5p upregulation was significantly associated with advanced TNM stage (P = .02), short recurrence-free (P = .005), and overall (P = .001) survivals. Importantly, miR-106b-5p expression was an independent predictor of poor prognosis (P < .05). RUNX3 was identified as a direct target gene of miR-106b-5p in HCC cells. Functionally, miR-106b-5p upregulation promoted the viability and invasion of HCC cells, while enforced RUNX3 expression reversed the oncogenic effects of miR-106b-5p overexpression.

Conclusions: miR-106b-5p may serve as a potent prognostic marker for tumor recurrence and survival of HCC patients. miR-106b-5p may exert an oncogenic role in HCC via regulating its target gene RUNX3.

Keywords: cell viability; hepatocellular carcinoma; invasion; microRNA-106b-5p; overall survival; recurrence-free survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Core Binding Factor Alpha 3 Subunit / genetics*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Staging
  • Prognosis
  • Survival Analysis
  • Up-Regulation*

Substances

  • Biomarkers, Tumor
  • Core Binding Factor Alpha 3 Subunit
  • MIRN106 microRNA, human
  • MicroRNAs
  • Runx3 protein, human